Stimulants like Ritalin can increase focus by restoring dopamine deficits

The relationship between fetal alcohol exposure and brain function is as complex as the brain itself. Recently, however, a study funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) may have found a common linkage - spontaneous activity of dopamine neurons - between prenatal alcohol exposure and attention-deficit/hyperactivity disorder (ADHD).

Although a mere three or four pounds in weight, the brain is composed of billions of nerve cells called neurons. Neurons communicate with each other at places called synapses by way of chemical messengers called neurotransmitters. Neurons generate electrical events called "action potentials" which cause neurotransmitters to travel across synapses, either "exciting" or "inhibiting" the "postsynaptic" or receiving cell. At any given moment, neurons are sending and/or receiving thousands of these messages. Scientists believe there are 100 or so different neurotransmitter varieties in the brain. Each neurotransmitter plays some role in most behaviors, but each neurotransmitter is often identified with a key behavior. Dopamine, for example, is strongly associated with motor system function, pleasure/reward, mental illness, craving and attention.

"The number of dopamine neurons isn’t necessarily important," said Roh-Yu Shen, Senior Scientist at the Research Institute on Addictions, State University of New York and lead author of the study published in the November issue of Alcoholism: Clinical & Experimental Research. "What’s important is how many of them are active."

Researchers gave pregnant rats varied doses of ethanol during gestation. They then studied the effects of this exposure on the spontaneous activity of dopamine neurons in the midbrain area of the offspring. In normal animal brains, said Shen, about 50 percent of the dopamine neurons are spontaneously active. The exact proportions are unknown for human brains but the same principle applies: higher levels of spontaneous activity may allow the brain to focus whereas lower levels of activity, also called "hypofunction," may be related to an inability to focus and accompanying hyperactivity. Shen’s study found that prenatal alcohol exposure significantly reduced the number of spontaneously active dopamine neurons in the midbrain area of both young (three to five months old) and adult (14 to 16 months old) male offspring. This finding suggests both immediate as well as long-lasting effects on the brain’s ability to focus.

"This is a very interesting finding within a very important field of study," said Jaime L. Diaz-Granados, Assistant Professor of Psychology and Neuroscience and Director of the Graduate Program in Neuroscience at Baylor University. "Dr. Shen’s finding has serious implications for both children with FAS-induced ADHD as well as those children whose ADHD is not FAS induced. For the latter group, we may find there are some dopamine abnormalities underlying ADHD."

"Understanding how fetal alcohol exposure can, at the very least, contribute to ADHD," said Shen, "allows us to understand the cellular mechanisms of what’s happening in the brain. This can lead us to tools that may improve our treatment strategy." Much of what is "known" about the treatment of attention-deficit disorder, said Shen, is based on trial and error rather than what she called "rational science."

"We already know from previous studies that stimulants like Ritalin," she said, "can restore deficits in dopamine systems. But now we need to ‘fine tune’ that strategy in terms of different drugs and dosages. We need to best understand how to restore activity."

Shen believes future research needs to focus more on the midbrain activity of dopamine neurons instead of their subsequent release into the forebrain area, in order to understand the real reasons for diminished dopamine activity. "We would like people to understand that not only alcohol exposure, cocaine exposure, and even lead exposure in the early stages can decrease the activity of dopamine neurons. If people understand that attention-deficit disorder and hyperactivity can have environmental causes during fetal development, maybe these disorders can be avoided."

Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.